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Aim: The study investigated psychiatrists' views towards the issue of medication discontinuation for patients in remission from first-episode psychosis in four countries (Hong Kong, Korea, Singapore and Japan) that are part of the Asian Network for Early Psychosis, focusing on whether the views of these countries differ with one another., Methods: A questionnaire was distributed to psychiatrists for completion. The questionnaire contained three sections: direct questions probing at views on medication discontinuation, case vignettes to assess applied decision-making and a checklist of criteria psychiatrists may view as necessary for the patient to satisfy before discontinuation. Total of 484 psychiatrists (97 from Hong Kong, 88 from Korea, 64 from Singapore and 233 from Japan) completed the questionnaire., Results: We found that (a) Asian psychiatrists believed that 1% to 19% of remitted patients can discontinue medication, an estimation that was lower than Western psychiatrists; (b) in agreement with clinical guidelines, Asian psychiatrists believed that patients should remain on medication for at least 1 to 2 years following the absence of psychotic symptoms; (c) "Absence of any relapsing episode following first episode" was considered the most important criterion when making a decision; and (d) there were significant differences in clinicians' perceptions across the four countries: for instance, Korean psychiatrists were more conservative with the duration of antipsychotics maintenance, while Singaporean psychiatrists were more open-minded towards clinical trials., Conclusions: Culture and social norms appear to determine the relative importance of factors that psychiatrists might consider during the decision-making process, thereby producing variations in the views held in different countries., (© 2018 John Wiley & Sons Australia, Ltd.)

Subjective quality of life (SQoL) has been increasingly studied in first-episode psychosis (FEP). Prior research primarily examined the impact of psychiatric symptoms on SQoL. Relationship between treatment-related factors and SQoL is under-studied. In this study, 159 Chinese patients who had completed 2-year treatment from early intervention service in Hong Kong were recruited. Assessments on premorbid adjustment, clinical profiles including social anxiety measure, functioning, antipsychotic-induced extrapyramidal side-effects and attitude toward medication treatment were conducted. SQoL was evaluated by Chinese version SF36 which generated mental and physical component summary (MCS and PCS) scores for analysis. Our results showed that more severe positive symptoms, higher level of depression, greater social anxiety, more negative attitude toward antipsychotic medications and greater degree of akathisia independently predicted lower MCS score. Higher social anxiety level and poorer functioning predicted lower PCS score. Our results indicate that affective and positive symptoms, functioning, and treatment-related variables are critical determinants of SQoL in FEP patients. These identified factors thus represent potentially malleable therapeutic targets for early detection and prompt intervention to promote enhancement of SQoL in the early stage of illness., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Aim: This study compared the quality of life and functioning of 285 first-episode psychosis Chinese patients with different antipsychotic medications in Hong Kong., Method: Under the Jockey Club Early Psychosis project, a total of 285 patients were recruited from all inpatient and outpatient psychiatric units in Hong Kong between 2009 and 2011. In addition to the medication information, patients were assessed with the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Udvalg for Kliniske Undersøgelser (UKU), Barnes Akathisia Rating Scale (BARS), the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale, and the Medical Outcomes Study Short Form 12-Item Health Survey (SF-12) after stabilization of mental condition. Differences between individual antipsychotic medications were compared using anova and multinomial regression model., Results: The results demonstrated significant differences between different antipsychotic medications in the mean of UKU neurological subscore, BARS total score, SOFAS score and SF-12 Mental Component Summary (MCS) score. Patients with haloperidol had higher mean UKU neurological subscore than patients with olanzapine or amisulpride. Risperidone was associated with higher mean BARS total score than olanzapine, amisulpride or sulpiride. Higher mean MCS was found in patients with amisulpride than patients with risperidone., Conclusions: The findings suggest that antipsychotics have differential associations with the quality of life and functioning in patients with first-episode psychosis. Future prospective study is warranted to investigate if patients with first-episode psychosis will benefit specific type of antipsychotics more than the others., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: Relapse is distressingly common after the first episode of psychosis, yet it is poorly understood and difficult to predict. Investigating changes in cognitive function preceding relapse may provide new insights into the underlying mechanism of relapse in psychosis. We hypothesized that relapse in fully remitted first-episode psychosis patients was preceded by working memory deterioration., Method: Visual memory and verbal working memory were monitored prospectively in a 1-year randomized controlled trial of remitted first-episode psychosis patients assigned to medication continuation (quetiapine 400 mg/day) or discontinuation (placebo). Relapse (recurrence of positive symptoms of psychosis), visual (Visual Patterns Test) and verbal (Letter-Number span test) working memory and stressful life events were assessed monthly., Results: Remitted first-episode patients (n = 102) participated in the study. Relapsers (n = 53) and non-relapsers (n = 49) had similar baseline demographic and clinical profiles. Logistic regression analyses indicated relapse was associated with visual working memory deterioration 2 months before relapse [odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19-7.92, P = 0.02], more stressful life events 1 month before relapse (OR 2.11, 95% CI 1.20-3.72, P = 0.01) and medication discontinuation (OR 5.52, 95% CI 2.08-14.62, P = 0.001)., Conclusions: Visual working memory deterioration beginning 2 months before relapse in remitted first-episode psychosis patients (not baseline predictor) may reflect early brain dysfunction that heralds a psychotic relapse. The deterioration was found to be unrelated to a worsening of psychotic symptoms preceding relapse. Testable predictors offer insight into the brain processes underlying relapse in psychosis.

Background: The long-term outcome of never-treated patients with schizophrenia is unclear., Aims: To compare the 14-year outcomes of never-treated and treated patients with schizophrenia and to establish predictors for never being treated., Method: All participants with schizophrenia (n = 510) in Xinjin, Chengdu, China were identified in an epidemiological investigation of 123 572 people and followed up from 1994 to 2008., Results: The results showed that there were 30.6%, 25.0% and 20.4% of patients who received no antipsychotic medication in 1994, 2004 and 2008 respectively. Compared with treated patients, those who were never treated in 2008 were significantly older, had significantly fewer family members, had higher rates of homelessness, death from other causes, being unmarried, living alone, being without a caregiver and poor family attitudes. Partial and complete remission in treated patients (57.3%) was significantly higher than that in the never-treated group (29.8%). Predictors of being in the never-treated group in 2008 encompassed baseline never-treated status, being without a caregiver and poor mental health status in 1994., Conclusions: Many patients with schizophrenia still do not receive antipsychotic medication in rural areas of China. The 14-year follow-up showed that outcomes for the untreated group were worse. Community-based mental healthcare, health insurance and family intervention are crucial for earlier diagnosis, treatment and rehabilitation in the community., (© The Royal College of Psychiatrists 2015.)

Aim: Non-adherence to medication is a common and significant challenge to successful treatment of psychosis. Knowledge of prescribed antipsychotic medication may influence psychosis patients' willingness to adhere to prescriptions. This study aimed to assess knowledge of psychosis patients on their prescribed antipsychotic medication with regard to drug name, type, dosage, purpose, side effects and reasons for taking medication, so as to investigate the associations between knowledge and adherence. The study also aimed to evaluate patient attitudes towards the current Chinese name of 'anti-psyche drug' for antipsychotic medication in Hong Kong, and survey patients' opinions on alternative names for antipsychotic medication., Methods: A questionnaire was administered to 70 consecutive patients from the psychiatric ward and outpatient clinic at Queen Mary Hospital in Hong Kong., Results: Current knowledge of Hong Kong psychosis patients falls short in areas of drug name (51.4% unaware), drug type (40% unaware) and prescribed dosage (28.6% unaware). The rate of self-reported non-adherence in the study sample was 38.6%. Adherence to medication was found to be positively associated with knowledge of purpose for taking medication. The current Chinese name 'anti-psyche drug' had a rating of 47/100 among psychosis patients., Conclusion: Measures should be taken to improve patient knowledge in areas of drug name, type and prescribed dosage. Reminding patients about the purpose of medication may also benefit adherence and overall treatment. Finally, because of the possible stigma of the current name of antipsychotic medication, an alternative term may be more favourable in promoting its acceptance in Hong Kong., (© 2014 Wiley Publishing Asia Pty Ltd.)

Background: The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP-outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined., Objective: To explore the relationship between DUP and long-term symptomatic remission., Methods: This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤30days), medium (31-180days) and long (>180days) DUP groups., Results: The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission., Conclusion: The findings support the threshold theory that DUP longer than 30days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication., Method: Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year., Results: Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms., Conclusion: Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group., (© 2013 Elsevier B.V. All rights reserved.)

Background: Cognitive impairment is a core feature of schizophrenia. Its relationship with duration of untreated psychosis (DUP), a potentially malleable prognostic factor, has been less studied, with inconsistent findings being observed in the literature. Previous research investigating such a relationship was mostly cross-sectional and none of those prospective studies had a follow-up duration beyond 2 years. Method A total of 93 Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. DUP and pre-morbid adjustment were measured using a structured interview incorporating multiple sources of information. Psychopathological evaluation was administered at intake, after clinical stabilization of the first psychotic episode, and at 12, 24 and 36 months. Cognitive functions were measured at clinical stabilization, and at 12, 24 and 36 months., Results: DUP exerted differential effects on various cognitive domains, with memory deficits being the most related to DUP even when potential confounders including pre-morbid adjustment and sex were adjusted. Prolonged DUP was associated with more severe impairment in visual memory at clinical stabilization and verbal memory at 24 and 36 months. Further, patients with a long DUP were found to have worse outcomes on negative symptoms at 36 months. The effects of DUP on verbal memory remained significant even when negative symptoms were taken into consideration., Conclusions: Our findings provided further supportive evidence that delayed treatment to first-episode psychosis is associated with poorer cognitive and clinical outcomes. In addition, DUP may specifically affect memory function and its adverse impact on verbal memory may only become evident at a later stage of the recovery process.

Objective: Relapses in psychosis are costly and may have irreversible consequences. Relapse prevention is thus critical in the treatment of schizophrenia. Apart from medication discontinuation, a consistent relapse predictor has not been identified due to limitations in previous studies. We aim to investigate relapse predictors in a large cohort of patients with first-episode psychosis., Method: This is a retrospective cohort study designed to evaluate relapses in first-episode psychosis patients in 3 years. A total of 1400 patients' case records were retrieved from a hospital database. Potential relapse predictors including demographic variables, baseline clinical measures, medication adherence, and residual positive symptoms upon clinical stabilization were collected., Results: The cumulative relapse rates were 19.3% by year 1, 38.4% by year 2, and 48.1% by year 3. Multivariate Cox-proportional hazards regression analysis revealed that medication non-adherence, smoking, schizophrenia diagnosis, younger age, and shorter baseline hospitalization were associated with an increased risk of relapse in 3 years., Conclusions: Nearly half of patients relapsed after 3 years following their first-episode psychosis. Smoking as a predictor of relapse is an intriguing new finding supportive of a link between nicotinic receptors and the dopamine system. Their relationship deserves further investigations with potential clinical implications for relapse prevention.

Aim: Existing clinical guidelines have not yet identified an optimal duration of maintenance antipsychotic drug treatment for stable, remitted first-episode psychosis patients. This study compares the perception of relapse risk and attitudes towards maintenance medication among professionals in nursing and social work fields who have direct clinical experience with first-episode psychosis patients. We explore a perception model that identifies the decision-making factors in the clinical dilemma between relapse and maintenance., Methods: A specially designed survey addressing perceptions of relapse risk and optimal duration of maintenance treatment was conducted among 63 experienced health-care professionals (30 nurses and 33 social workers) in the field of early psychosis in Hong Kong., Results: Two clinically relevant themes were identified that affected professionals' judgment on the optimal duration of maintenance treatment in stable, remitted first-episode psychosis patients: (i) the remission period; and (ii) professionals' perceptions of relapse risk involved in medication discontinuation. The remission period was a significant predictor of the perceived relapse risk. Compared with social workers, mental health nurses perceived a higher relapse risk for patients before Bonferroni adjustment., Conclusions: The three key clinical components discussed--remission period, perceived relapse risk and perceived optimal duration of maintenance treatment--are interconnected, collectively influencing health-care professionals' attitudes towards relapse and maintenance for patients. Our study identified differences between the perceptions of nursing and social work professionals, indicating a need for communication and discussion among professional groups in order to arrive at a coherent, efficacious team consensus., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Purpose of Review: Psychosis is among the most frequent psychiatric symptoms in late life. Treatment of late life psychosis is often challenging because of age-related changes, physical comorbidities and frailty of older adults. The present study aims at reviewing recent literature on pharmacological treatment of psychosis in the older population., Recent Findings: Recent studies show that antipsychotics remain the mainstay of treatment for older adults with psychosis. Although the efficacies of both typical and atypical antipsychotics have been demonstrated in older adults with schizophrenia, delirium and Parkinson's disease psychosis, there is a growing body of data favoring atypical antipsychotics. However, most of the evidence is not based on rigorously conducted trials. In addition, the use of antipsychotic medication in managing psychosis associated with dementia has declined significantly with the recognition of its serious adverse effects in this vulnerable population. A recent study suggests that effective alternative treatments are yet to be developed., Summary: Studies have demonstrated the clinical benefits of antipsychotics in older people with psychosis. The potential benefits from the use of antipsychotics must be weighed against their adverse effects.

Aim: Although phase-specific early intervention for first-episode psychosis has been implemented in many different parts of the world, limited medium-term outcome data are available in non-Western populations with relatively low mental health resources. The study aimed to determine the effectiveness of phase-specific early intervention in first-episode psychosis., Method: In this cohort study, we compared the 3-year outcome of 700 first-episode psychosis patients who received phase-specific early intervention with that of 700 patients matched for age, sex and diagnosis who received standard psychiatric care prior to early intervention. Using a structured data acquisition procedure, we determined functional outcome, symptom levels, relapse, recovery, suicidal behaviour and service utilization from clinical records., Results: Patients in the early intervention group had longer full-time employment or study (P<0.001), fewer days of hospitalization (P<0.001), less severe positive symptoms (P=0.006), less severe negative symptoms (P =0.001), fewer suicides (P=0.009) and fewer disengagements (P=0.002) than the historical control group. Additionally, more patients in the early intervention group experienced a period of recovery (P=0.001), but the two groups had similar rates of relapse (P=0.08) and durations of untreated psychosis (P=0.72)., Conclusions: The 3-year outcome in phase-specific early intervention compared favourably with that of standard psychiatric care, particularly with respect to functional outcome and reduction in hospitalizations, suicides and disengagements. However, intervention did not appear to reduce the rate of relapse., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Introduction: Medication adherence is critical to the management of psychotic disorder. Different factors associated with medication adherence have been investigated in previous studies. However, the association with subjective weight perception, which is related to the weight gain side effect of antipsychotics, has not been thoroughly investigated. Subjective weight perception may not equal objective weight status. This study tests the hypothesis that medication adherence is related to subjective weight perception in a group of patients with first-episode psychotic disorder who have taken antipsychotics for one year., Methods: This study recruited 160 participants with one-year histories of first-episode psychotic disorder and measured their actual and perceived weights, amount of weight gain in the past year, body size satisfaction and medication adherence levels. The associations between medication adherence and both the actual and perceived weight status were analyzed controlling for other confounding factors including insight, drug attitude, illness severity and other medication side effects., Results: Stepwise multiple regression analysis found that the participants' perceived weight status, negative attitude toward their drugs and insight were the major factors associated with poor medication adherence. Of the participants who perceived themselves as being overweight, 86% believed that antipsychotics were responsible. Among those who had such beliefs, 72% had reduced their antipsychotic dosages on their own. About half of the participants had gained more than 7% of their baseline weight and 43.1% of the participants were found to be overweight after one year of treatment with antipsychotics., Conclusions: The results of this study indicate that medication adherence is associated with perceived weight status. Healthcare professionals should be aware of this relationship and address this issue early in the management of patients. Apart from weight management programs, education on a correct weight perception should be carried out with the promotion of proper drug attitudes and better insight for the improvement of medication adherence in the early course of psychotic disorder.

Objective: To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment., Design: 12 month randomised, double blind, placebo controlled trial., Setting: Early psychosis outpatient clinics in Hong Kong., Participants: 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis., Interventions: Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred., Main Outcome Measure: Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds., Results: 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07)., Conclusion: In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.

Aim: This article aims to describe the Hong Kong experience in developing and implementing an early psychosis programme., Methods: In 2001, the Early Assessment Service for Young People with Psychosis programme was launched in Hong Kong, providing both educational and service components. Public education includes promotion of timely help-seeking, accessible channels to service and knowledge of psychosis. The 2-year phase-specific intervention includes intensive medical follow-up and individualized psychosocial intervention. The programme has adopted the case-management approach, in which case managers provide protocol-based psychosocial intervention. The programme collaborates with non-governmental organizations and community networks in the provision of rehabilitation service., Results: An average of over 600 young patients enter the programme for intensive treatment each year. Based on preliminary data from a 3-year outcome study, patients in the programme have remarkable reductions in hospital stay accompanied by improvements in vocational functioning., Conclusions: The results suggested that the programme improved patients' outcome. Additional costs such as extra medical staff and medications may be offset by the shortened hospital stay. Further directions in early intervention are also discussed.

Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine-antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effectiveness in clinical research and the implications of research for the health care delivery system. Although a rationale for CAP can be developed from receptor pharmacology, there is little available preclinical research testing these concepts in animal models. Randomized clinical trials of CAP show minimal or no benefit for overall severity of symptoms. Most studies at the level of health services are limited to estimates of CAP prevalence and some suggestion of increased costs. Increasing use of antipsychotic polypharmacy in general may be a factor contributing to the under-utilization of clozapine and long delays in initiating clozapine monotherapy. Translational research models can be applied to clinical questions such as the value of CAP. Better linkage between the components of translational research may improve the appropriate use of medications such as clozapine in psychiatric practice.

Background: Anti-psychotic treatment appears to be associated with striatal volume increase, but how early this change occurs is still unknown., Methods: A single prospective cohort of 20 anti-psychotic-naïve patients, newly diagnosed with schizophrenia, underwent magnetic resonance imaging brain scan at baseline. This was repeated following up to 8 weeks of anti-psychotic treatment. Ten patients had repeat scan within only 3 weeks. The choice of anti-psychotic medication was naturalistic, i.e., clinician-led. Well-matched healthy individuals were also scanned to control for non-specific changes over a 3-week period., Results: After 3 weeks of anti-psychotic treatment, significant grey matter volume increase in the right caudate, superior and inferior frontal gyrus, precentral gyrus, and left inferior parietal lobule was noted. However, after 8 weeks of anti-psychotic treatment, volume increase in the right thalamus and bilateral cerebellum was observed. Significant grey matter reduction was detected in the left medial frontal gyrus at both 3- and 8-week intervals., Conclusions: Early increase in striatal volume change occurs as early as 3 weeks after anti-psychotic treatment, whilst thalamic volume increase is apparent later, by 8 weeks of treatment. We speculate that drug-mediated neuroplasticity may provide a biomarker for clinical recovery.

Objective: Over the last 15 years, a focus on early intervention in psychotic disorders has emerged. Initially, the early psychosis movement focused on timely recognition and phase-specific treatment of first-episode psychosis. However, early psychosis researchers suspected that pushing the point of intervention even further back to the prodromal phase of psychotic disorders may result in even better outcomes. This article reviews intervention research in the ultra-high-risk phase of psychotic disorders., Data Sources: A literature search of intervention trials with ultra-high-risk cohorts published after 1980 was conducted on PubMed with the search terms prodrome and intervention., Study Selection: All published intervention trials with ultra-high-risk cohorts., Data Synthesis: The first generation of intervention trials indicated that both pharmacologic and psychological intervention strategies may be of value in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder., Conclusions: Further controlled intervention trials with larger sample sizes are required in order to confirm and extend these findings. We argue that the clinical staging model provides a framework for the rationale and design of such studies, with simpler, safer, and more benign interventions being better candidates for first-line treatment, while more complex and potentially harmful treatments should be reserved for those cases in which response has failed to occur. Recent evidence indicates that neuroprotective agents, such as essential fatty acids, may be a suitable form of intervention for the ultra-high-risk phase of psychotic disorders, with a positive risk-benefit balance. Ethical aspects have become more salient given the recently observed declining transition rate in ultra-high-risk samples. We outline the key questions for the next generation of ultra-high-risk intervention trials., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Background: We and others have reported that patients experiencing their first episode of psychosis already have significant structural brain abnormalities. Antipsychotics seem to reverse subcortical volume deficits after months of treatment. However, the early impact of medication on brain morphology is not known., Method: Forty-eight individuals in their first episode of psychosis underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were antipsychotic naive and 22 were newly treated with antipsychotic medication for a median period of 3 weeks. In each group, 80% of subjects received a diagnosis of schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity, height, years of education, paternal socio-economic status (SES) and Positive and Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey matter were compared voxel by voxel, using Brain Activation and Morphological Mapping (BAMM) software. We also conducted testing of group differences with region-of-interest (ROI) measurements of the caudate nucleus., Results: Relative to the untreated group, those receiving antipsychotic medication for 3-4 weeks had significantly greater grey-matter volumes in the bilateral caudate and cingulate gyri, extending to the left medial frontal gyrus. ROI analysis confirmed that, in treated patients, the right and left caudate nuclei were significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed) respectively., Conclusions: Early striatal grey-matter enlargement may occur within the first 3-4 weeks of antipsychotic treatment. Possible reasons for putative striatal hypertrophy and its implications are discussed.

Objective: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine., Methods: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight., Results: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores., Conclusion: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity.

Objective: Adherence to antipsychotic treatment is an important aspect of the long-term management of schizophrenia. The evaluation of adherence is often difficult in the clinical setting. This study compared patient self-reporting and clinician judgment of adherence behaviour in patients with early and chronic schizophrenia., Method: Clinician-rated questionnaires and parallel patient self-rated questionnaires were administered to 229 patients with early schizophrenia (illness duration < 5 years) and 255 patients with chronic schizophrenia. Items in the questionnaires addressed two forms of adherence behaviour (forgetting to take medication and deciding to stop medication) as well as attitudes toward medication., Results: Significant non-adherent behaviour was reported by patients, particularly in the early schizophrenia group. Non-adherent behaviour was related to feelings of embarrassment about taking medication. Both non-adherence and embarrassment were under-recognized by clinicians. Starting from a prior probability of 0.24, knowledge of the patients' attitudes increased the posterior probability to 0.33, whereas clinicians' detection of non-adherence (deciding to stop medication) improved the posterior probability to 0.65. When both clinicians' evaluations and patients' attitudes were known, the posterior probability improved to 0.68., Conclusion: Non-adherence is a widespread phenomenon in early schizophrenia. Increasing clinicians' sensitivity to patients' feelings of embarrassment may be an important factor in the detection of non-adherence. When taking a base rate of non-adherence into consideration, clinicians' evaluations appeared to be more effective in detecting non-adherence than simple information obtained from patients on their attitudes toward medication. Pragmatic real-life estimation of non-adherence has important implications for the possibility of intervention.

Objective: Adherence to antipsychotic treatment is an important aspect of long term management of schizophrenia and other related psychotic disorders. The evaluation of adherence is often difficult in clinical settings. This study compared patients self-reports and clinician judgment of adherence behavior and explored their relationship with attitudes toward taking medication., Methods: Clinician rated questionnaire and matching patient self rated questionnaires were administered to 508 consecutive outpatients and their clinicians in four hospital clinic sites in Hong Kong. Items in the questionnaires address adherence behaviors as well as attitudes toward medication. In addition, clinicians also estimate the presence of factors unfavorable to adherence such as substance abuse, cognitive impairments etc., Results: Non-adherence was reported in at least 26% of patients. Clinician's detection of non-adherence behaviors achieved relative high specificity (0.84) but has low sensitivity (0.33). A logistic regression analysis on patients' decision to stop medication revealed that significant predictors include patients' reported lack of perception from the benefits of medication, patients' reported negative feelings associated with regular medication and younger age., Conclusion: Non-adherence is a widespread phenomenon affecting a significant proportion of outpatients under treatment. Clinicians have relatively low sensitivity in detecting which patients are non-adherent. Non-adherence behavior is predicted by level of awareness of illness, perceived benefits of medication, negative feelings toward medication and age.

Background: The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known., Methods: In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning., Results: A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, -7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups., Conclusions: In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584)., (Copyright 2006 Massachusetts Medical Society.)